Pharmacokinetic Comparability of Benralizumab Using Accessorized Pre-Filled Syringe or Autoinjector in Healthy Volunteers

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02968914
• Collaborator: Parexel (Industry)
• Enrollment: 180
• Locations: 2
• Arms: 2
• Actual Duration (Months): 6.2
• Patients Per Site: 90
• Patients Per Site Per Month: 14.4

Study Details

Study Description

Brief Summary

An open-label, single dose Pharmacokinetic (PK) comparability study to demonstrate comparable drug exposure following Subcutaneous benralizumab administration by using accessorized pre-filled syringe (APFS) or autoinjector (AI) devices.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Chronic Obstructive Pulmonary Disease	Biological: Benralizumab; Biological: Benralizumab	Phase 1

Detailed Description

A study of descriptive comparison of benralizumab PK by weight and injection site.

This study will be a multicenter, randomized, open-label, parallel group Phase 1 study designed to compare benralizumab PK exposure in healthy subjects following single subcutaneous (SC) administration of fixed 30 mg dose of benralizumab by using APFS and single-use AI. Eligible subjects will be healthy subjects aged 18 to 55 years, with a body weight of 55 to 100 kg and a body mass index of 18 to 29.9 kg/m2 . A total of 180 subjects will be randomized. Randomization will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg), and within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS or AI) with injection site (upper arm, abdomen or thigh), presented in Table 1. This study will be performed at 2 study centers.

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 Pharmacokinetic Comparability Study of Benralizumab Administrated Using Accessorized Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers.
• Actual Study Start Date: Jan 4, 2017
• Actual Primary Completion Date: Jul 13, 2017
• Actual Study Completion Date: Jul 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Benralizumab by Accessorized Pre-Filled Syringe Drug administration by Accessorized Pre-Filled Syringe. A total of 180 subjects will be randomized and will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg). Within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS) with injection site (upper arm, abdomen or thigh)	Biological: Benralizumab; A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.
Other: Benralizumab by Autoinjector Drug administration by Autoinjector A total of 180 subjects will be randomized and will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg). Within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS) with injection site (upper arm, abdomen or thigh)	Biological: Benralizumab; A humanized, afucosylated, monoclonal antibody (mAb) that binds specifically to the human IL-5 receptor alpha subunit (IL-5Rα) on the target cell.

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-time Curve From Zero to Infinity (AUCinf) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices

2. Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices

3. Maximum Observed Concentration (Cmax) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices

Secondary Outcome Measures

1. Time When Maximum Concentration is Observed (Tmax) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges

2. Terminal Half-life (t½) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.

3. Apparent Extravascular Clearance (CL/F) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To evaluate the CL/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.

4. Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) [At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.

5. Number of Participants With Adverse Events [At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57]

   To evaluate safety and tolerability of Benralizumab

6. Antidrug Antibody (ADA) Status [At predose (Day 1), Days 29 and 57]

   To evaluate the immunogenicity of Benralizumab

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male and/or female subjects of non-child-bearing potential aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.

• Females must be non pregnant,non lactating and non-child-bearing potential, confirmed at screening

• Sexually active male willingness to use contraception

• Body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 55 kg and no more than 100 kg inclusive.

Exclusion Criteria:

• History of any clinically significant disease, severe allergy/anaphylaxis to any biologic therapy, Guillain-Barré syndrome, smoking and alcohol or drug abuse

• Diagnosis of helminth parasitic infection and acute upper or lower respiratory infections

• Disorders related to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment

• Alanine aminotransferase/aspartate aminotransferase level ≥1.5 times the upper limit of normal

• White blood cell count and neutrophils < lower limit of normal

• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP)

• Positive result for serum hepatitis B surface antigen or anti-Hemoglobin C (anti-HBc) antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

• Intake of new chemical entity (not been approved for marketing) within 3 months of the first administration of investigational product

• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening

• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent

• Receipt of any marketed (e.g., omalizumab, mepolizumab etc.) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent

• Receipt of live attenuated vaccines 30 days prior to randomization on Day 1

• Current malignancy, or history of malignancy except (basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix)

• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.

• Use of antacids, analgesics (except paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer

• Previous receipt of received benralizumab

• Any ongoing or recent minor medical complaints

• Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Berlin		Germany	14050
2	Research Site	Harrow		Germany	HA1 3UJ

Sponsors and Collaborators

• AstraZeneca
• Parexel

Investigators

• Principal Investigator: Dr. Rainard Fuhr, Medicine, PAREXEL Early Phase Clinical Unit Berlin
• Principal Investigator: Dr. Pablo Forte-Soto, PAREXEL Early Phase Clinical Unit London

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 4, 2017
• Study Protocol - Jul 7, 2017

More Information

Additional Information:

• SAP
• SP

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02968914
• Other Study ID Numbers: D3250C00030
• First Posted: Nov 21, 2016
• Last Update Posted: Jul 5, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by AstraZeneca: Asthma; Chronic Obstructive pulmonary Disease; Pharmacokinetics; Healthy volunteers
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Benralizumab

Study Results

Participant Flow

Recruitment Details	Subjects who met all the inclusion and none of the exclusion criteria were enrolled at PAREXEL Early Phase Clinical Unit in Berlin and London.
Pre-assignment Detail	Subjects attended a Screening Visit within 28 days before receiving their first dose of Benralizumab. All subjects underwent inclusion exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study-related procedures.

Arm/Group Title	Benralizumab 30mg Autoinjector (AI)	Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS)
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Period Title: Overall Study
STARTED	90	90
COMPLETED	90	90
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Benralizumab 30mg Autoinjector (AI)	Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS)	Total
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.	Total of all reporting groups
Overall Participants	90	90	180
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.8 (10.8)	41.1 (11.1)	40.9 (10.9)
Sex: Female, Male (Count of Participants)
Female	17 18.9%	16 17.8%	33 18.3%
Male	73 81.1%	74 82.2%	147 81.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.1%	2 2.2%	3 1.7%
Not Hispanic or Latino	89 98.9%	88 97.8%	177 98.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.2%	3 3.3%	5 2.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 5.6%	5 5.6%	10 5.6%
White	83 92.2%	80 88.9%	163 90.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 2.2%	2 1.1%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve From Zero to Infinity (AUCinf)
Description	To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	88	87
Geometric Mean (Geometric Coefficient of Variation) [day·ng/mL]	72210 (29.7)	76220 (32.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg AI, Benralizumab 30mg AFPS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio (%)
	Estimated Value	94.46
	Confidence Interval	(2-Sided) 90%; 88.16 to 101.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Description	To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	90	90
Geometric Mean (Geometric Coefficient of Variation) [day·ng/mL]	60560 (27.3)	65230 (29.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg AI, Benralizumab 30mg AFPS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio (%)
	Estimated Value	92.83
	Confidence Interval	(2-Sided) 90%; 87.41 to 98.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Maximum Observed Concentration (Cmax)
Description	To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	90	90
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	2096 (32.7)	2269 (35.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg AI, Benralizumab 30mg AFPS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio (%)
	Estimated Value	92.34
	Confidence Interval	(2-Sided) 90%; 86.34 to 98.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time When Maximum Concentration is Observed (Tmax)
Description	To evaluate the Tmax of Benralizumab administered to various injection sites and in subjects with different body weight ranges
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects who received benralizumab for whom PK blood samples were assumed not to be affected by factors such as protocol violations (e.g., disallowed medications or incomplete dose administration) and who had at least one post dose quantifiable serum PK observation.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	90	90
Abdomen 55.0 to 69.9 kg	4.59	6.06
Abdomen 70.0 to 84.9 kg	6.98	5.98
Abdomen 85.0 to 100.0 kg	5.06	6.96
Thigh 55.0 to 69.9 kg	4.00	4.52
Thigh 70.0 to 84.9 kg	4.05	3.52
Thigh 85.0 to 100.0 kg	4.59	4.03
Upper arm 55.0 to 69.9 kg	6.97	4.96
Upper arm 70.0 to 84.9 kg	7.00	5.02
Upper arm 85.0 to 100.0 kg	7.00	6.97

5. Secondary Outcome

Title	Terminal Half-life (t½)
Description	To evaluate the t½ of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all the subjects as defined for above endpoint. For Benralizumab 30mg AI, two subjects and for Benralizumab 30mg AFPS, three subjects were excluded from the PK analysis set.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	88	87
Abdomen 55.0 to 69.9 kg	18.83 (24.9)	20.15 (21.8)
Abdomen 70.0 to 84.9 kg	20.22 (21.0)	17.43 (21.7)
Abdomen 85.0 to 100.0 kg	19.59 (19.9)	21.04 (21.7)
Thigh 55.0 to 69.9 kg	18.58 (20.6)	19.72 (21.4)
Thigh 70.0 to 84.9 kg	19.93 (23.4)	18.28 (17.9)
Thigh 85.0 to 100.0 kg	19.02 (19.9)	17.30 (11.5)
Upper arm 55.0 to 69.9 kg	22.46 (13.6)	17.30 (26.9)
Upper arm 70.0 to 84.9 kg	20.54 (14.0)	20.16 (25.3)
Upper arm 85.0 to 100.0 kg	19.01 (26.9)	19.42 (26.3)

6. Secondary Outcome

Title	Apparent Extravascular Clearance (CL/F)
Description	To evaluate the CL/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all the subjects as defined for above endpoint. For Benralizumab 30mg AI, two subjects and for Benralizumab 30mg AFPS, three subjects were excluded from the PK analysis set.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	88	87
Abdomen 55.0 to 69.9 kg	388.8 (34.3)	388.9 (43.8)
Abdomen 70.0 to 84.9 kg	462.9 (29.5)	508.9 (33.2)
Abdomen 85.0 to 100.0 kg	504.6 (18.3)	402.7 (30.4)
Thigh 55.0 to 69.9 kg	350.1 (32.6)	281.1 (16.8)
Thigh 70.0 to 84.9 kg	393.7 (29.6)	325.9 (18.2)
Thigh 85.0 to 100.0 kg	378.2 (26.8)	406.0 (22.9)
Upper arm 55.0 to 69.9 kg	345.8 (24.7)	455.2 (29.8)
Upper arm 70.0 to 84.9 kg	429.4 (19.5)	366.1 (27.0)
Upper arm 85.0 to 100.0 kg	532.6 (21.7)	471.6 (20.3)

7. Secondary Outcome

Title	Apparent Volume of Distribution Based on the Terminal Phase (Vz/F)
Description	To evaluate the Vz/F of Benralizumab administered to various anatomical injection sites and in subjects with different body weight ranges.
Time Frame	At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all the subjects as defined for above endpoint. For Benralizumab 30mg AI, two subjects and for Benralizumab 30mg AFPS, three subjects were excluded from the PK analysis set.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	88	87
Abdomen 55.0 to 69.9 kg	10.56 (28.0)	11.30 (28.4)
Abdomen 70.0 to 84.9 kg	13.50 (30.4)	12.79 (25.5)
Abdomen 85.0 to 100.0 kg	14.26 (25.0)	12.22 (15.8)
Thigh 55.0 to 69.9 kg	9.386 (18.2)	7.999 (15.5)
Thigh 70.0 to 84.9 kg	11.32 (23.5)	8.596 (13.5)
Thigh 85.0 to 100.0 kg	10.38 (20.2)	10.13 (21.0)
Upper arm 55.0 to 69.9 kg	11.21 (21.2)	11.36 (17.7)
Upper arm 70.0 to 84.9 kg	12.72 (23.6)	10.65 (18.7)
Upper arm 85.0 to 100.0 kg	14.61 (23.0)	13.21 (32.9)

8. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	To evaluate safety and tolerability of Benralizumab
Time Frame	At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

Safety set consisted of all subjects who received at least 1 dose of Benralizumab were included in the safety analysis for the study.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	90	90
Any AE	50 55.6%	46 51.1%
Death	0 0%	0 0%
Any SAE	0 0%	0 0%
Any AE leading to discontinuation	0 0%	0 0%

9. Secondary Outcome

Title	Antidrug Antibody (ADA) Status
Description	To evaluate the immunogenicity of Benralizumab
Time Frame	At predose (Day 1), Days 29 and 57

Outcome Measure Data

Analysis Population Description

Safety set consisted of all subjects who received at least 1 dose of Benralizumab were included in the safety analysis for the study.

Arm/Group Title	Benralizumab 30mg AI	Benralizumab 30mg AFPS
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.	All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
Measure Participants	90	90
ADA prevalence (positive at any visit)	2 2.2%	6 6.7%
ADA incidence	0 0%	3 3.3%

Adverse Events

Time Frame	At pre-dose and 2 h post-dose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
Arm/Group Title	Benralizumab 30mg Autoinjector (AI)		Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS)
Arm/Group Description	All randomized subjects received 30mg Benralizumab by AI under fasted conditions.		All randomized subjects received 30mg Benralizumab by APFS under fasted conditions.
All Cause Mortality
	Benralizumab 30mg Autoinjector (AI)		Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/90 (0%)
Serious Adverse Events
	Benralizumab 30mg Autoinjector (AI)		Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Benralizumab 30mg Autoinjector (AI)		Benralizumab 30mg Accessorized Pre-filled Syringe (AFPS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/90 (55.6%)		46/90 (51.1%)
Cardiac disorders
Cardiovascular symptom	0/90 (0%)		1/90 (1.1%)
Palpitations	0/90 (0%)		1/90 (1.1%)
Ear and labyrinth disorders
Ear pain	1/90 (1.1%)		0/90 (0%)
Excessive cerumen production	0/90 (0%)		1/90 (1.1%)
Eye disorders
Eye pruritus	1/90 (1.1%)		0/90 (0%)
Eye swelling	0/90 (0%)		1/90 (1.1%)
Ocular hyperaemia	0/90 (0%)		1/90 (1.1%)
Gastrointestinal disorders
Toothache	4/90 (4.4%)		3/90 (3.3%)
Abdominal pain	1/90 (1.1%)		2/90 (2.2%)
Nausea	2/90 (2.2%)		1/90 (1.1%)
Vomiting	3/90 (3.3%)		0/90 (0%)
Diarrhoea	1/90 (1.1%)		1/90 (1.1%)
Abdominal discomfort	1/90 (1.1%)		0/90 (0%)
Abdominal pain upper	0/90 (0%)		1/90 (1.1%)
Dyspepsia	1/90 (1.1%)		0/90 (0%)
Frequent bowel movements	0/90 (0%)		1/90 (1.1%)
General disorders
Fatigue	5/90 (5.6%)		1/90 (1.1%)
Influenza like illness	1/90 (1.1%)		1/90 (1.1%)
Asthenia	0/90 (0%)		1/90 (1.1%)
Discomfort	0/90 (0%)		1/90 (1.1%)
Feeling hot	1/90 (1.1%)		0/90 (0%)
Injection site hypersensitivity	1/90 (1.1%)		0/90 (0%)
Pyrexia	1/90 (1.1%)		0/90 (0%)
Immune system disorders
Seasonal allergy	0/90 (0%)		1/90 (1.1%)
Infections and infestations
Nasopharyngitis	18/90 (20%)		13/90 (14.4%)
Rhinitis	2/90 (2.2%)		0/90 (0%)
Gingivitis	1/90 (1.1%)		0/90 (0%)
Myringitis	0/90 (0%)		1/90 (1.1%)
Tonsillitis	0/90 (0%)		1/90 (1.1%)
Injury, poisoning and procedural complications
Sunburn	2/90 (2.2%)		1/90 (1.1%)
Limb injury	1/90 (1.1%)		1/90 (1.1%)
Traumatic haematoma	1/90 (1.1%)		0/90 (0%)
Investigations
Body temperature increased	0/90 (0%)		1/90 (1.1%)
Metabolism and nutrition disorders
Decreased appetite	1/90 (1.1%)		0/90 (0%)
Musculoskeletal and connective tissue disorders
Back pain	3/90 (3.3%)		1/90 (1.1%)
Arthralgia	2/90 (2.2%)		0/90 (0%)
Neck pain	1/90 (1.1%)		1/90 (1.1%)
Muscle spasms	0/90 (0%)		1/90 (1.1%)
Muscle tightness	0/90 (0%)		1/90 (1.1%)
Musculoskeletal chest pain	0/90 (0%)		1/90 (1.1%)
Musculoskeletal pain	0/90 (0%)		1/90 (1.1%)
Pain in extremity	1/90 (1.1%)		0/90 (0%)
Periarthritis	1/90 (1.1%)		0/90 (0%)
Tendon discomfort	0/90 (0%)		1/90 (1.1%)
Nervous system disorders
Headache	14/90 (15.6%)		5/90 (5.6%)
Dizziness	2/90 (2.2%)		0/90 (0%)
Disturbance in attention	0/90 (0%)		1/90 (1.1%)
Hypertonia	0/90 (0%)		1/90 (1.1%)
Syncope	1/90 (1.1%)		0/90 (0%)
Tension headache	1/90 (1.1%)		0/90 (0%)
Psychiatric disorders
Insomnia	0/90 (0%)		1/90 (1.1%)
Listless	1/90 (1.1%)		0/90 (0%)
Sleep disorder	1/90 (1.1%)		0/90 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	7/90 (7.8%)		11/90 (12.2%)
Cough	1/90 (1.1%)		5/90 (5.6%)
Dyspnoea	0/90 (0%)		2/90 (2.2%)
Nasal dryness	0/90 (0%)		1/90 (1.1%)
Rhinorrhoea	0/90 (0%)		1/90 (1.1%)
Skin and subcutaneous tissue disorders
Acne	2/90 (2.2%)		2/90 (2.2%)
Rash	1/90 (1.1%)		0/90 (0%)
Skin fissures	1/90 (1.1%)		0/90 (0%)
Vascular disorders
Haematoma	2/90 (2.2%)		2/90 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All clinical study findings and documents will be regarded as confidential. The investigator and members of his/her research team must not disclose such information without prior written approval from the sponsor.